The specific aim of this project is to carry out a detailed analysis of the relationship between the structure of growth hormone and its growth-promoting activity. This systematic study will be done on a comparative basis using human and porcine growth hormones. These hormones will be subjected to partial degradation by enzymes and to other chemical modifications. As far possible, in each instance, the nature of the chemical change and the chemical characteristics of the products will be established. The biological characterization of these products in animal systems and in man should yield information about the relationship of certain activities of growth hormone, for example, the diabetogenic activity, to the growth-promoting activity and to structure. Since an effort will be made to work with reasonably well- characterized products, the information obtained from all experiments, positive and negative, should be of value. A good many derivatives of the hormones will be finally screened in human subjects. To do this efficiently, one or more relatively simple, reliable, dose-related responses of human subjects will be required, and a subsidiary aim of this project has been to determine which responses can be obtained and used routinely in human subjects. Hopefully, these studies will lead to the identification of the minimum structure required for growth-promoting activity in man and animals. The structure may be such that a derivative active in man may be produced from animal hormones by relatively simple chemical or enzymatic means. If the common active structure is in fact simple, it may be possible to synthesize it in relatively large amounts.